The emergence of a six-layered neocortex is one of the hallmarks of mammalian brain evolution. An important feature of the neocortex is its ability to change throughout a lifetime. This plasticity is especially pronounced during development. Developmental plasticity is a highly adaptive process that allows the neocortex to functionally optimize both its organization and connectivity to match the physical parameters of the environment in which an animal develops. While we appreciate that the developing cortex is highly malleable, the limits to which it can be altered and recover following injury, or extreme environmental rearing conditions is still not fully understood. The goals of this R21 proposal are to: 1) determine the extent to which the entire cortical sheet can re-organize and recover following severe loss of tissue very early in development;2) determine the developmental stage at which the cortex loses, or has a reduced capacity to recover following a lesion;and 3) quantify the extent to which prolonged exposure to a highly specified visual environment can influence the organization and connectivity of the developing cortex, and ultimately the behavior in normal and brain lesioned individuals. In these experiments in short-tailed opossums, bilateral ablations of visual cortex will be made just before thalamocortical afferents reach the cortex or just after thalamocortical innervation of the cortex has occurred. Animals will be reared in either a neutral or visually enhanced environment until adulthood. To determine the effects of this environment in both normal and lesioned animals, behavioral tests will be administered and the functional organization and connectivity of spared cortex will be determined in these same animals. These experiments will allow us to probe the limits of plasticity in normally developing systems as well as to appreciate the extent to which individuals can recover from large early lesions to the neocortex. The results of our studies will have a significant clinical impact in terms of prognosis for recovery from injuries that occur at different developmental time points, and rehabilitation strategies that facilitate recovery in children with early cortical insult. PUBLIC HEALTH RELEVANCE: The goal of the present investigation is to determine the extent to which the cortex and the behavior it generates can recover following neonatal lesions to visual cortex. By rearing animals in an enhanced visual environment, we hope to push the limits of recovery in brain lesioned animals, and ultimately generate normal visually mediated behavior in these individuals. These studies have important implications for children who sustain early cortical lesions or trauma and will aid in prognosis, and impact rehabilitation strategies that facilitate recovery.